Effect of Androgens on Serum Lipids and Lipoproteins 1

A N T A L SOLYOM, 2 Laboratory of Neurochemistry,

National Institute of Neurological Diseasesand Stroke,
National Institutes of Health, Bethesda, Maryland 20014

ABSTRACT is one of the most potent anabolic steroids

known.
The effects of androgens on lipid Testosterone is bound to a protein compo-
transport and metabolism have been re-
nent of the chromatin at the site of active RNA
viewed. These effects are probably inde-
synthesis within the nuclei of accessory sex
pendent of the androgenic and anabolic tissues. This occurs after conversion of testo-
activities of the androgens, although the sterone by nuclear 5a-reductase into dihydro-
molecular mechanism of action is still not testosterone (5a-androstanolone), which ap-
known. Presumably the lowering by an- pears to be the active form of testosterone in
drogens of the concentrations of serum these tissues (1). However in nontarget tissues,
lipids and lipoproteins could be the con- e.g., liver, metabolites other than dihydro-
sequence possibly of a primary, inhib- testosterone are formed when testosterone is
itory effect on the synthesis of apolipo- incubated with nuclei or cytoplasm. These
protein A. In addition the role of in- results indicate that the metabolic actions of
creased lipolytic activities in plasma and androgens are mediated possibly through diffe-
of effects on intermediary metabolism rent metabolites in different tissues.
has been considered.
The intermediary metabolism of testoster-
one proceeds essentially via three main reac-
INTRODUCTION tions (Fig. 1): (a) 17/3-hydroxysteroid dehydro-
Androgens are steroids known for their g e n a s e ( 1 7 - / 3 - h y d r o x y s t e r o i d : N A D / N A D P
anabolic and masculinizing effects. Androgen- 17-/3-oxydoreductase, EC 1.1.1. j/k): oxidation
icity refers to an anabolic effect on the sex of the 17~-hydroxy group resulting in 17-keto-
organs and on cell differentiation, while in the steroid formation (andostenedione); (b) A4-5ot-
common usage of the term an anabolic effect or A4-5/3-reductase: reduction of the 4,5-double
signifies the extragenital stimulation of protein bond in ring A (2 isomers); (c) 3o~- and
synthesis. Testosterone, the male sex hormone, 3/3-hydroxysteroid dehydrogenase (3-ot-hydrox-
ysteroid: NAD(P) oxydoreductase, EC
1One of eight papers presented at the symposium 1. l. 1.5 0, and 3-/3-hydroxysteroid:NAD(P)
"Recent Advances in Drugs Affecting Lipid Metabo- oxydoreductase, EC 1.1.1.51): formation of
lism," AOCS Meeting, Houston, May 1971. the 3-hydroxy-5-androstan-17-one metabolites
2Special Fellowship Awardee ( I F l l NSO2245-01) (4 isomers).
from the National Institute of Neurological Diseases These reactions describe two pathways
and Stroke.
through which the metabolites of testosterone
are formed: the "17-oxo" and the "17-
RELATIVE ANDROGENICITY OF TESTOSTERONE METABOLITES hydroxyl" pathways. The androgenicity of the
1 7 - h y d r o x y l metabolites are significantly
"'17-oxo" pathway "17 hydroxyl" pathway
greater than that of the corresponding 17-oxo
17~-hydroxy-
steroid- compounds (2). Among the metabolites with
dehydrogenase ring A saturated, the 5a isomers are the
ANDROSTENEDIONE TESTOSTERONE biologically important ones. Furthermore in
20% 100%
females and in prepubertal males or in male
r 5~- and 52 5a- and 5~. l
~ reductases reductases hypogonadism, testosterone is metabolized pre-
dominantly along the "17-oxo" pathway. In
ANDROSTANEDIONE 5~ ANOROSTANOLONE
? 90%
males after puberty testosterone metabolism
proceeds mainly via the "17-hydroxyl" path-
i 3o.- and i~ ~ - and ~ I
hydroxysteroid hydroxysteroid i way (3). The substitution of an alkyl group in
dehydrogenase dehydrogenase I~
the 17a-position prevents the oxidation of the
ANOROSTERONE (Sa] 5a-ANDROSTANEDIOL 1 7~3-hydroxy g r o u p . Methyltestosterone
10% 60%
AETIOCHOLANOLONE (5#} ( 17a-methyl-1 713-hydroxyandrost-4-en-3-one) is
0%
unique among 17a-substituted alkyl derivatives
in retaining androgenic potency when given
FIG. 1. Pathway of testosterone metabolism. The
percentage values indicate the relative androgenicity of orally. Other chemical modifications of testo-
testosterone metabolites. sterone caused significant dissociation of andro-

100
 EFFECT OF ANDROGENS ON SERUM LIPIDS 101

TABLE I
Effect of Androgenic and Anabolic Steroids on Serum Lipid and Lipoprotein Levels a
Serum lipoproteins
Serum VLDL LDL HD L
Steroids Species lipids (pre-~) 03) (a) Reference

Testosterone Man U I D 13
D D 14
Dog D D 15
D 16
Rat U 17
17-a-Methyl-testosterone Man U I D 13
1 I D 18
D I D 19
D D I D 12
Dog D D 15
D D D 20
D D D 21
D D D D 22
Rat D D D 23
Androsterone Man D 24
D (I) D 25
19-Nor-testosterone Man D (I) O 26
A1-Testololactone Man D U D 27
17a-Methyl-androstenediol Man D D 14
17 ~-Methyl- 5~-an drostane diol Dog D 28

aU=unchanged; D=deereased; I=increased. VLDL = very low density lipoproteins. LDL = low density lipopro-
teins. HDL = high density lipoproteins.

genic a n d a n a b o l i c activities (4), i n d i c a t i n g t h a t t h e p o t e n t p r o g e s t i n n o r e t h i n d r o n e , w h i c h is

these biological effects of t h e a n d r o g e n s are n o t
i n h e r e n t l y related.
EFFECTS ON L I P I D M E T A B O L I S M
D u r i n g p u b e r t y t h e s u b c u t a n e o u s fat de-
creases in m a l e s b u t n o t in females, a n d
e u n u c h s have a t e n d e n c y t o obesity. These
d e v e l o p m e n t s suggest t h a t a n d r o g e n s affect
adipose tissue m e t a b o l i s m . In fact p r o l o n g e d
a d m i n i s t r a t i o n of high doses of t e s t o s t e r o n e or
m e t h y l a n d r o s t e n e d i o l r e p o r t e d l y decrease the
t o t a l fat c o n t e n t of the b o d y (5,6). F u r t h e r -
m o r e t r e a t m e n t of fasting female rats or cas-
t r a t e d male rats w i t h t e s t o s t e r o n e causes a
m a r k e d increase in t h e p l a s m a c o n c e n t r a t i o n s
of free f a t t y acids, possibly reflecting a d i r e c t
f a t - m o b i l i z i n g activity of the a n d r o g e n s (7,8).
A d m i n i s t r a t i o n of s y n t h e t i c anabolic steroids,
such as 1 9 - n o r - a n d r o s t e n o l o n e ( D u r a b o l i n ) a n d
methandrostenolone (Dianabol), reproduced
t h e t e s t o s t e r o n e eftect. H o w e v e r t h e same
a u t h o r s (8) f o u n d t h a t e s t r o g e n s increased
plasma levels of free f a t t y acids as well, a n d
w h e n estrogens were a d m i n i s t e r e d t o g e t h e r
w i t h a n d r o g e n s t h e y acted synergistically.
R e c e n t l y it was f o u n d (9) t h a t the a d m i n i s -
t r a t i o n of the s y n t h e t i c a n d r o g e n o x a n d r o l o n e
increased t h e p o s t h e p a r i n lipolytic activities in
h u m a n plasma, w i t h c o n c o m i t t a n t d i m i n u t i o n
of the p l a s m a level of triglycerides. H o w e v e r
only mildly a n d r o g e n i c , h a d similar effects.
I n h e a l t h y adult s u b j e c t s sex d i f f e r e n c e s are
e v i d e n t in the c o n c e n t r a t i o n s of s e r u m lipids
a n d l i p o p r o t e i n s : in m e n m o r e c i r c u l a t i n g lipid
is in t h e f o r m of l o w e r d e n s i t y l i p o p r o t e i n s
t h a n is t h e case in w o m e n , whereas w o m e n have
m o r e high d e n s i t y l i p o p r o t e i n s t h a n m e n
( 1 0,1 1). F u r t h e r m o r e a d m i n i s t r a t i o n of gonadal
h o r m o n e s c h a r a c t e r i s t i c a l l y alters the levels o f
lipids a n d p a t t e r n s of l i p o p r o t e i n s in the s e r u m
(12). In general a n d r o g e n s d i m i n i s h the c o n c e n -
t r a t i o n of high d e n s i t y l i p o p r o t e i n s , b o t h in
m a n and in e x p e r i m e n t a l animals. In m a n this
effect is a c c o m p a n i e d b y u n c h a n g e d or in-
creased c o n c e n t r a t i o n s of low d e n s i t y l i p o p r o -
teins, and b y decreased c o n c e n t r a t i o n s of very
low d e n s i t y l i p o p r o t e i n s . In the d o g a n d rat
a d m i n i s t r a t i o n o f t e s t o s t e r o n e or m e t h y l t e s t o s -
t e r o n e also lowers the c o n c e n t r a t i o n of low
d e n s i t y l i p o p r o t e i n s . A l t h o u g h s e r u m levels of
c h o l e s t e r o l m a y n o t c h a n g e significantly in
h e a l t h y subjects, t h e h y p o c h o l e s t e r o l e m i c a n d
h y p o l i p e m i c effect of m e t h y l t e s t o s t e r o n e and
o t h e r t e s t o s t e r o n e anologs has b e e n well docu-
m e n t e d in lipemic patients. T h e data clearly
i n d i c a t e t h a t n o t only m e t h y l t e s t o s t e r o n e , b u t
analogs of t e s t o s t e r o n e w i t h significantly l o w e r
a n d r o g e n i c activity, e x e r t the same e f f e c t o n
s e r u m l i p o p r o t e i n s . In a d d i t i o n a m a j o r fecal
m e t a b o l i t e of m e t h y l t e s t o s t e r o n e , 1 7 a - m e t h y t -
5(x-androstane-3/3, 17~-diol, w h i c h is a w e a k e r

LIPIDS, VOL. 7, NO. 2

 102 A. SOLYOM
androgen than the parent compound, repro-
duces completely the hypocholesterolemic ef-
fect of methyltestosterone in dogs (Table I).
A possible interrelationship between andro-
gen metabolism and serum lipid levels may be
illustrated by a consideration of certain patho-
logical states. The association of serum lipid
abnormalities with thyroid dysfunction is well
known. In thyrotoxicosis low and high density
lipoproteins and serum lipid levels are de-
creased, whereas in hypothyroid subjects low
density lipoproteins and lipid levels are increased
(29-32). Moreover in myxoedema there is a fall
in the excretion of total androgens attributable
mainly to a diminution of androsterone compo-
nent (33). Determination of the androsterone to
aetiocholanolone urinary excretion ratio is use-
ful for obtaining information on the relative
activities of 5a- and 5/3-reductases. A decrease
in this ratio indicates the relative or absolute
diminution of the biologically active 5a-
reduced products of both the "17-oxo" and
"17-hydroxyl" pathways of testosterone meta-
bolism, i.e., androsterone and 5a-androstane-
diol. This is the case in myxoedema (33), after
corticosteroid administration (34), in hyper-
lipemic patients including familial hypercholes-
terolemia (35), and in myocardial infarction
(36), i.e., when serum lipid levels are generally
increased. On the other hand, in thyrotoxicosis
higher androgenic activity can be expected
from the increased ratio (33) which coincides
with lower serum lipid levels. The relationship
between the kinetics of testosterone metabo-
lism and thyroid function provides further
support for the possibility that the effect of the
thyroid on lipid metabolism is mediated, at
least in part, through androgens. Hyperthyroid-
ism is associated with increased plasma concen-
tration of testosterone, whereas in hypo-
thyroidism the serum testosterone concentra-
tion is decreased (37). All these findings agree
with the previous observation that in myxoe-
dema the hyperlipemia can be ameliorated by
the administration of androsterone (24,25).
Androgens may also influence carbohydrate
metabolism and thereby affect lipid metabo-
lism. Low excretion of dehydroepiandrosterone
has been reported in diabetic patients with
obesity (38). This androgen inhibits glucose-6-
phosphate dehydrogenase (39). It was postula-
ted, therefore, that lower level of dehydro-
epiandrosterone would result in higher enzyme
activity and consequently increased synthesis of
NADPH. This latter effect could account for an
increment in the synthesis of fatty acids and
other lipids. Furthermore administration of
dehydroepiandrosterone reduces serum lipid
levels in man (40) and in rat (41). In hyper-
LIPIDS, VOL. 7, NO. 2
lipemic patients the plasma level and the
urinary excretion of dehydroepiandrosterone is
lower, and a significant reciprocal correlation
between plasma phospholipid levels and urinary
excretion of this steroid has been established
(35).
To explain the hypolipemia and hypocholes-
terolemia caused by androgens a limited num-
ber of investigations have also evaluated the
effect of androgens on cholesterol biosynthesis
and metabolism. In rats methyltestosterone
produces a significant decrease in hepatic
synthesis of cholesterol, but this response is
compensated by a significant increase in intes-
tinal cholesterol synthesis, and total cholesterol
biosynthesis in these tissues remains unaltered
(42). The oxidation of cholesterol to biliary
and fecal bile acids is not increased significantly
in rats treated with methyltestosterone (43).
The observation that methyltestosterone de-
creases the incorporation of acetate into serum
cholesterol in the dog (21) may provide an
explanation for the changes in cholesterol
metabolism, but this in itself is inadequate to
account for the marked decrease which has
been demonstrated in all three major lipid
classes.
EFFECT ON S E R U M A P O L I P O P R O T E I N S
In recent studies in dogs we investigated the
possibility that a primary effect on the metabo-
lism of apolipoproteins is the mechanism by
which androgens lower the concentrations of
serum lipids and lipoproteins. The distribution
of apolipoprotein components in canine serum
was determined by immunochemical means,
and we estimated that the characteristic protein
components of the high density lipoproteins,
designated as apolipoprotein A, may comprise
as much as 90% of total apolipoproteins (44).
L i p o p r o t e i n s of the density range of
1.110-1.250 g/ml contain only apolipoprotein
A, and this high density lipoprotein fraction
was used to study the effect of methyltesto-
sterone on the metabolism of apolipoprotein A.
Methyltestosterone produces an increment in
albumin concentration and decrement in a 1-
and /3-globulins, without altering total protein
levels in serum (22). At the same time it causes
a reduction of the apolipoprotein and lipid
concentrations of all density classes of lipopro-
teins in canine serum. Although no qualitative
changes have been demonstrated by immuno-
chemical analyses, marked diminution in the
quantity of all high density lipoprotein compo-
nents is observed. The amino acid composition
of apolipoprotein A is not altered appreciably,
a finding that suggests that methyltestosterone
 EFFECT OF ANDROGENS ON SERUM LIPIDS
produces a quantitative rather than a qualitative
change in apolipoprotein A. The diminution in
low density lipoproteins comprises a propor-
tionately greater reduction in lipoproteins con-
taining apolipoprotein A than in those contain-
ing apolipoprotein B. The metabolic studies,
carried out in the same four dogs before and
during methyltestosterone treatment, have
demonstrated that the relative amount of
C14-1ysine incorporated into the apolipopro-
teins of high density and low density lipopro-
teins is reduced, whereas that incorporated into
albumin is increased. To evaluate the half-lives
and rates of turnover of these proteins, C 14-
albumin and high density lipoproteins contain-
ing C 14-apolipoprotein A were obtained from a
donor dog given C14-1ysine. In whole serum
and within the high density lipoproteins meth-
yltestosterone reduces the mean turnover rate
and the total exchangeable pool for apolipo-
protein A to less than 50% of controls. The
half-time for the disappearance of apolipopro-
tein A from serum is not significantly changed
by the treatment. The rate of turnover of
albumin increases almost threefold and the
total exchangeable pool by almost 50% during
methyltestosterone treatment, while the half-
life decreased. These findings demonstrate that
methyltestosterone decreases synthesis of
apolipoprotein A and increases synthesis of
albumin (45).
The effects of androgens on the metabolism
of individual serum proteins are u n k n o w n .
However the available data on the changes in
concentrations of serum proteins clearly imply
that individual proteins are affected differently
and that there is no uniform anabolic action of
androgens with regard to serum proteins. The
finding of the increase in albumin concentra-
tion and decrease in apolipoprotein A and
H-globulin concentrations during methyltestos-
terone treatment in the dog (22) is supported
by the recent report on the semiquantitative
immunochemical evaluation of the effects of
testosterone administration on serum protein
concentrations in the domestic fowl (46). More-
over in man androgen treatment increases the
concentration of thyroxine-binding pre-albumin
(47), and may diminish the concentration of
thyroxine-binding al-globulin (47,48). On the
basis of the findings described above, these
changes in serum protein concentrations may
reflect a differential effect of androgens on the
synthesis of serum proteins in the liver. If a
primary action on the synthesis of apolipopro-
tein A is indeed responsible for the hypolipemic
effects of androgens, this finding would mean
that the anabolic and hypotipemic activities are
mediated through different mechanisms.
103
MECHANISM OF ACTION
Our present understanding of the mechanism
whereby androgens affect serum lipids and
lipoproteins is very limited. The possible and in
part speculative explanations for the findings of
the clinical and experimental animal investiga-
tions reviewed above will be offered by discuss-
ing the questions below.
I. Are the biological e~fects of androgens,
namely the androgenicity, anabolic activity and
hypolipemic effect, mediated through the same
mechanism or metabolite, i.e., are these effects
inherently related? The data already discussed
suggest that almost certainly they are not. This
conclusion implies the possibility of finding a
particular testosterone metabolite or a synthe-
tic steroid, or both, which will selectively affect
lipid metabolism.
lI. Which are the possible points of action
of androgens on lipid metabolism? (a) Mobiliza-
tion of free fatty acids from adipose tissue may
increase. As a result levels of free fatty acids in
plasma would increase, with a possible c o n s e -
quent increased synthesis of triglycerides in the
liver. However this action in itself, if indeed
operative, would tend to be hyperlipemic rather
than hypolipemic. A decrease in the fat content
of the body may also be the consequence
because of the increased fatty acid utilization.
(b) The increase in plasma lipoprotein lipase
activity, or postheparin lipolytic activity in
general, should increase the breakdown of
triglycerides and the utilization of fatty acids.
This action could account for an increase in
plasma levels of free fatty acids and the
decreased plasma level of triglyceride. In addi-
tion a possible increase in the turnover of
triglycerides might be predicted, especially if an
increased mobilization of free fatty acids is also
taken into account. (c) Carbohydrate metabo-
lism might be affected, e.g., by an inhibitory
action on glucose-6-phosphate dehydrogenase,
in such a way that a decrease in lipid synthesis
would result. This action could contribute to
the decrease of both the fat c o n t e n t of the
body and the serum levels of lipids. (d) Inhibi-
tion of cholesterol biosynthesis in liver or
intestine, or both, could explain the hypocho-
lesterolemic action, but would be insufficient as
the initial event to account for the other
effects. It may well be the consequence, how-
ever, of the actions mentioned under points (c)
and (e). (e) Selective inhibition of the synthesis
of apolipoprotein A may explain the decreased
concentration in the plasma of the high density
lipoproteins. It could possibly account also for
other effects, as discussed below.
III. Which of the androgen effects on lipid
LIPIDS, VOL. 7, NO. 2
104 A. SOLYOM
m e t a b o l i s m m i g h t be e x p l a i n e d b y a selective
i n h i b i t i o n of the s y n t h e s i s o f a p o l i p o p r o t e i n A?
(a) T h e decrease in the c o n c e n t r a t i o n o f h i g h
d e n s i t y l i p o p r o t e i n s ( o b s e r v e d in m a n , d o g a n d
rat) m a y b e the c o n s e q u e n c e of d i m i n u t i o n in
the p r o d u c t i o n of these l i p o p r o t e i n s in t h e
liver. T h e increased ratio of c h o l e s t e r o l to p r o t e i n
in t h e high d e n s i t y l i p o p r o t e i n s in m a n (12)
m a y reflect a p r i m a r y a l t e r a t i o n in t h e p r o t e i n
m o i e t y in the l i p o p r o t e i n s . (b) T h e increase in
t h e c o n c e n t r a t i o n of low d e n s i t y l i p o p r o t e i n s in
m a n m a y reflect the increased b r e a k d o w n o f
,-ery low d e n s i t y l i p o p r o t e i n triglyceride b y
increased lipolytic activities or b e c a u s e trans-
p o r t of relatively m o r e lipid in this class m a y be
r e q u i r e d as a result o f t h e d i m i n u t i o n of
a p o l i p o p r o t e i n A, or b o t h . (c) T h e decrease in
t h e c o n c e n t r a t i o n of very l o w d e n s i t y l i p o p r o -
teins c o u l d be e x p l a i n e d b y an i n c r e a s e d lipo-
lytic activity in t h e plasma. T h e increase o f
p o s t h e p a r i n lipolytic activities o b s e r v e d i n
h u m a n p l a s m a m a y be i n d e p e n d e n t o f a m e c h a -
n i s m involving a p o l i p o p r o t e i n A. R e c e n t find-
ings ( 4 9 - 5 1 ) i n d i c a t e t h a t specific a p o l i p o p r o -
tein p e p t i d e s play the role of a c t i v a t o r s for
l i p o p r o t e i n lipase. T h e p e p t i d e s w h i c h corres-
p o n d to the a p o l i p o p r o t e i n A, i.e., t h e charac-
teristic m a j o r p e p t i d e s of high d e n s i t y l i p o p r o -
reins, are n o t activators. It is n o t k n o w n
w h e t h e r the c o n c e n t r a t i o n o f small a c t i v a t o r
p e p t i d e s ( w h i c h m a y be r e f e r r e d t o as p a r t s of
a p o l i p o p r o t e i n C) m i g h t increase d u r i n g a n d r o -
gen t r e a t m e n t . H o w e v e r it is t e m p t i n g to
speculate t h a t u n d e r physiological c o n d i t i o n s
the e n z y m e a c t i v a t i o n may d e p e n d n o t s i m p l y
o n the a b s o l u t e a m o u n t , b u t on t h e relative
p r o p o r t i o n o f certain a p o l i p o p r o t e i n peptides.
T h u s t h e d i m i n u t i o n of n o n a c t i v a t i n g pep-
tides f r o m a p o l i p o p r o t e i n A m i g h t correlate
w i t h increased lipolytic activities. (d) T h e
decrease o f c h o l e s t e r o l s y n t h e s i s o b s e r v e d in
dog a n d in rat m a y be e x p l a i n e d by the
r e c e n t f i n d i n g t h a t an a p o l i p o p r o t e i n , possibly
a p o l i p o p r o t e i n A, plays an essential role in t h e
p r o m o t i o n of h e p a t i c c h o l e s t e r o l b i o s y n t h e s i s
( 5 2 , 5 3 ) . (e) T h e decrease in the d o g o f all
serum lipid levels, i.e., c h o l e s t e r o l , p h o s p h o l i p i d
a n d triglyceride, m a y be e x p l a i n e d b y a possi-
bly c o o r d i n a t e d p r o d u c t i o n o f all c o m p o n e n t s
of high d e n s i t y l i p o p r o t e i n s , w i t h a p r i m a r y
role for the p r o t e i n m o i e t y in this p r o c e s s (54).
With regard to a p o l i p o p r o t e i n A, t h e levels o f
p h o s p h o l i p i d a n d c h o l e s t e r o l w o u l d be princi-
pally a f f e c t e d by this m e c h a n i s m . In a d d i t i o n
an increased c a t a b o l i s m of triglycerides c o u l d
explain the l o w e r i n g of p l a s m a levels o f triglyc-
erides. (f) T h e lack of d e v e l o p m e n t o f f a t t y
liver in the dog (15), a n d the p r o t e c t i v e a c t i o n
against the e t h i o n i n e - i n d u c e d f a t t y liver in rat
LIPIDS, VOL. 7, NO. 2
(55) m i g h t also be r e l a t e d t o t h e role apolipo-
p r o t e i n A m a y play in t h e r e g u l a t i o n o f t h e
s y n t h e s i s of the lipids i t t r a n s p o r t s , i]e., t h e
m a j o r i t y of p l a s m a lipids in t h e s e species. I n
c o n t r a s t a selective i m p a i r m e n t o f the s y n t h e s i s
o f a p o l i p o p r o t e i n B, as in t h e case of t r e a t m e n t
w i t h o r o t i c acid ( 5 6 ) , w o u l d be e x p e c t e d t o
cause f a t t y liver.
ACKNOWLEDGMENT
The original investigations by the author of this
review were carried out in collaboration with R.H.
Bradford and R.H. Furman at the Cardiovascular
Section of the Oklahoma Medical Research Founda-
tion, Oklahoma City, Oklahoma.
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[Received August 16, 1971]
LIPIDS, VOL. 7, NO. 2